Nebulizers, or atomizers as they are sometimes called, are devices that generate a fine spray or aerosol from a liquid. A particularly useful application for nebulizers is to provide a fine spray containing a dissolved or a suspended particulate drug for administration to a patient by inhalation.
Since the patient has to administer a certain amount of medication, the treatment time will be mainly determined by the mass flow rate of the aerosol generated by the nebulizer. Particularly for new medications, like biologics, the medication dose can be large, which means that the treatment time can be up to several hours for nebulizers that are currently on the market.
However, so-called flat plate technology or piezo-cavity-mesh based nebulizers have the potential to offer much higher mass flow rates than conventional nebulizers. In these types of nebulizers, a cavity for the liquid drug is created with an ultrasonic transducer forming one wall and the other opposing wall of the cavity comprising an aperture or mesh plate containing an array of nozzles or holes. When the transducer is activated, ultrasonic pressure waves are created in the liquid in the cavity, causing liquid in the cavity to be pushed through the nozzles to form fine droplets.
One significant disadvantage with this type of nebulizer, however, is that the mass flow rate achieved by the nebulizer is highly sensitive to the distance between the transducer and the mesh plate. The mass flow rate for a particular flat plate technology nebulizer as a function of the distance between the transducer and mesh plate is shown in FIG. 1. Thus, it can be seen that the mass flow rate halves when the separation (referred to as the ‘height’ in FIG. 1) between the transducer and mesh plate is 100 microns (0.1 mm) from the optimum separation (around 0.7 mm).
The mass flow rate should be the same for each and every nebulizer produced. Thus, a tolerance requirement is placed on nebulizers such that 90% of nebulizers built should have a mass flow rate within 25% of the target mass flow rate. This requirement can be fulfilled only when the tolerance of the separation distance is such that the standard deviation of this distance is on the order of 10 microns (0.01 mm).
In addition, since the patient is administering medication to his or her lungs, care needs to be taken to keep the nebulizer clean. Residue from the liquids used in the nebulizer can lead to fouling and could become a potential health hazard. Moreover, this residue can subsequently clog the nozzles in the mesh plate, decreasing the output performance of the nebulizer. For current nebulizers, it is recommended that the nebulizer is cleaned by rinsing with hot soapy water of 95° C. on a daily basis. This leads to a requirement for the nebulizer to be able to tolerate around 1800 of these cleaning cycles over its lifetime. Furthermore, the interior of the nebulizer should be easily accessible while at the same time any performance deterioration during the lifetime should be avoided. Therefore, a further desirable feature of the piezo-cavity-mesh type nebulizer is the ability to remove at least the mesh plate from the nebulizer for cleaning or replacement.
These requirements combined demand a nebulizer design that can be manufactured with very small tolerances, high stability, and of course, low cost. These demands are hard to meet with conventional manufacturing technologies like injection-molding.
Therefore, there is a need for an alternative nebulizer and method of manufacturing thereof that meet these requirements.